Sun Hong Yoo

Comparative study between doxorubicin-eluting beads and conventional transarterial chemoembolization for treatment of hepatocellular carcinoma.

BACKGROUND & AIMS Transarterial chemoembolization (TACE) is a widely used treatment for hepatocellular carcinoma. In order to maximize its therapeutic efficacy, doxorubicin-loaded drug-eluting beads have been developed to deliver higher doses of the chemotherapeutic agent and to prolong contact time with the tumor. The purpose of this study was to evaluate the efficacy and safety of drug-eluting bead (DC bead®) TACE in comparison with conventional TACE (cTACE). METHODS A total of 129 patients who underwent TACE between August 2008 and February 2011 were enrolled. We compared HCC patients who underwent TACE with DC bead® (n=60) to controls who received cTACE (n=69). The primary end points were treatment response and treatment-related adverse events. The secondary end point was time to progression. RESULTS The treatment response in the DC bead® group was significantly higher than that of the cTACE group (p<0.001). The time to progression was significantly better in the DC bead® group than in the cTACE group (11.7 and 7.6months, respectively, p=0.018). Subgroup analysis showed that in intermediate-stage HCC, DC bead® treatment resulted in a significantly better treatment response and longer time to progression than cTACE (p<0.001 and 0.038, respectively). However, there was no statistically significant difference in liver toxicity between the DC bead® and cTACE group (p>0.05). CONCLUSIONS TACE with DC bead® showed better treatment response and delayed tumor progression compared with cTACE. There was no significant difference in hepatic treatment-related toxicities. DC bead® TACE thus appears to be a feasible and promising approach to the treatment of HCC.

Role of intrahepatic tumor control in the prognosis of patients with hepatocellular carcinoma and extrahepatic metastases.

Background and Aim:  There has been little information about the long‐term outcome and prognostic factors in patients with hepatocellular carcinoma (HCC) and extrahepatic metastases. The purpose of this study was to investigate the clinical factors affecting survival after extrahepatic metastasis and to determine the survival benefit of controlling intrahepatic HCC.

Durability of viral response after off-treatment in HBeAg positive chronic hepatitis B

AIM To evaluate the durability in hepatitis B e antigen (HBeAg) positive chronic hepatitis B patients who discontinued antiviral treatment. METHODS A total of 48 HBeAg positive chronic hepatitis B patients who were administered nucleoside analogues and maintained virological response for ≥ 6 mo [hepatitis B virus (HBV) DNA < 300 copies/mL and HBeAg seroconversion] before cessation of treatment were enrolled between February 2007 and January 2010. The criteria for the cessation of the antiviral treatment were defined as follows: (1) achievement of virological response; and (2) duration of consolidation therapy (≥ 6 mo). After treatment cessation, the patients were followed up at 3-6 mo intervals. The primary endpoint was serologic and virologic recurrence rates after withdrawal of antiviral treatment. Serologic recurrence was defined as reappearance of HBeAg positivity after HBeAg seroconversion. Virologic recurrence was defined as an increase in HBV-DNA level > 10⁴ copies/mL after HBeAg seroconversion with previously undetectable HBV-DNA level. RESULTS During the median follow-up period of 18.2 mo (range: 5.1-47.5 mo) after cessation of antiviral treatment, the cumulative serological recurrence rate was 15 % at 12 mo. The median duration between the cessation of antiviral treatment and serologic recurrence was 7.2 mo (range: 1.2-10.9 mo). Of the 48 patients with HBeAg positive chronic hepatitis, 20 (41.6%) showed virological recurrence. The cumulative virologic recurrence rates at 12 mo after discontinuing the antiviral agent were 41%. The median duration between off-treatment and virologic recurrence was 7.6 mo (range: 4.3-27.1 mo). The mean age of the virological recurrence group was older than that of the non-recurrence group (46.7 ± 12.1 years vs 38.8 ± 12.7 years, respectively; P = 0.022). Age (> 40 years) and the duration of consolidation treatment (≥ 15 mo) were significant predictive factors for offtreatment durability in the multivariate analysis [P = 0.049, relative risk (RR) 0.31, 95% CI (0.096-0.998) and P = 0.005, RR 11.29, 95% CI (2.054-65.12), respectively]. Patients with age (≤ 40 years) who received consolidation treatment (≥ 15 mo) significantly showed durability in HBeAg positive chronic hepatitis B patients (P = 0.014). These results suggest that additional treatment for more than 15 mo after HBeAg seroconversion in patients who are ≤ 40 years old may be beneficial in providing a sustained virological response. CONCLUSION Our data suggest that HBeAg seroconversion is an imperfect end point in antiviral treatment. Long-term consolidation treatment (≥ 15 mo) in younger patients is important for producing better prognosis in HBeAg positive chronic hepatitis B.

Should lamivudine monotherapy be stopped or continued in patients infected with hepatitis B with favorable responses after more than 5 years of treatment

Regarding the limited evidence for determining the optimal duration of antiviral treatment for hepatitis B, the long‐term outcome of patients with favorable responses to over 5 years of lamivudine monotherapy was investigated. Two hundred seventy‐one patients who had received lamivudine for at least 5 years were enrolled. Ultimately, 72 patients without YMDD mutations and showing hepatitis B virus (HBV) DNA levels <2.5 pg/ml after 5 years of treatment were analyzed. Mean treatment duration with lamivudine was 9.1 ± 2.6 years. During the treatment, HBeAg and HBsAg loss/seroconversion rates were 95 and 6.9%, respectively. Decompensation and hepatocellular carcinoma (HCC) developed in 2.8 and 6.9% of patients, respectively. Old age and cirrhosis were risk factors for HCC development. Finally, 11.1% of patients developed YMDD mutations after 8.3 ± 2.4 years of treatment. There was no hepatic decompensation among the patients who developed delayed YMDD mutations. Sixteen patients who achieved a complete response stopped lamivudine and four patients showed relapses 10.3 ± 8.5 months after stopping lamivudine. Relapsed patients had more cirrhotic livers and higher rates of HBeAg positivity at 5 years than patients who maintained complete response. The present study suggests that patients who do not develop YMDD mutations over 5 years of treatment with lamivudine may continue lamivudine monotherapy until the loss of HBsAg. However, even for the patients showing favorable response over 5 years of treatment, those in older ages, with cirrhosis or who show poor HBeAg responses should be on careful monitoring to detect the development of viral mutations, relapse and even HCC. J. Med. Virol. 85:34–42, 2012.

DC Bead Transarterial Chemoembolization Is Effective in Hepatocellular Carcinoma Refractory to Conventional Transarteral Chemoembolization: A Pilot Study

Background/Aims To determine if hepatocellular carcinoma refractory to conventional transarterial chemoembolization (TACE) responds to TACE with DC beads. Methods Between July 2008 to June 2010, 435 patients underwent TACE. Of these, 10 patients who had tumors refractory to conventional TACE and who thus were treated with TACE with DC beads were enrolled in this study. The treatment response after TACE with DC beads was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and the Response Evaluation Criteria in Cancer of the Liver (RECICL). Results Ten tumors were treated in 10 patients. Using the mRECIST and the RECICL, a complete response was observed in four (40%) of the tumors, and six tumors (60%) showed a partial response. Eight (80%) out of 10 HCCs showed delayed enhancement patterns upon angiography, and better responses were observed in these cases following DC bead treatment. The adverse effects of treatment with DC beads became tolerable. Conclusions TACE with DC beads was effective for HCCs refractory to conventional TACE, and this treatment elicited a better response, especially when the tumors were small and showed a delayed enhancement pattern upon angiography.

Differences in the patterns and outcomes of enhanced viral replication between hepatitis C virus and hepatitis B virus in patients with hepatocellular carcinoma during transarterial chemolipiodolization

Background/Aims Enhanced replication of hepatitis C virus (HCV) is well described in the setting of moderate to severe immunosuppression. The aims of this retrospective study were to determine the incidence of enhanced HCV replication in hepatocellular carcinoma (HCC) patients undergoing transarterial chemolipiodolization (TACL) and to identify the factors associated with enhanced replication of HCV. The clinical pattern of enhanced HCV replication was compared with hepatitis B virus (HBV) reactivation during TACL. Methods This study enrolled 49 anti-HCV-seropositive patients who were diagnosed with HCC between January 2005 and December 2010 and who underwent TACL using epirubicin and/or cisplatin with consecutive HCV RNA copies checked. For comparison, 46 hepatitis B surface antigen1-positive patients with HCC who were treated with TACL were also enrolled. The frequency, associated factors, and clinical outcomes of enhanced HCV replication were analyzed and compared with those of HBV reactivation during TACL. Results Enhanced replication of HCV occurred in 13 (26.5%) of the 49 anti-HCV-seropositive patients during TACL. Of these 13 patients, 4 developed hepatitis, but none of the subjects developed decompensation due to the hepatitis. No significant clinical factors for enhanced HCV replication during TACL were found. Compared with HBV reactivation, the frequency of hepatitis attributed to enhanced HCV replication was significantly lower than that for HBV reactivation (8.2% vs. 23.9%, P=0.036). Conclusions TACL can enhance HCV replication; however, the likelihood of hepatitis and decompensation stemming from enhanced HCV replication was lower than that for HBV reactivation in patients undergoing TACL.

Preemptive antiviral therapy with entecavir can reduce acute deterioration of hepatic function following transarterial chemoembolization

Background/Aims Hepatic damage during transarterial chemoembolization (TACE) is a critical complication in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Apart from its role in preventing HBV reactivation, there is some evidence for the benefits of preemptive antiviral therapy in TACE. This study evaluated the effect of preemptive antiviral therapy on acute hepatic deterioration following TACE. Methods This retrospective observational study included a prospectively collected cohort of 108 patients with HBV-related HCC who underwent TACE between January 2007 and January 2013. Acute hepatic deterioration following TACE was evaluated. Treatment-related hepatic decompensation was defined as newly developed encephalopathy, ascites, variceal bleeding, elevation of the bilirubin level, prolongation of prothrombin time, or elevation of the Child-Pugh score by ≥2 within 2 weeks following TACE. Univariate and multivariate analyses were conducted to identify factors influencing treatment-related decompensation. Preemptive antiviral therapy involves directing prophylaxis only toward high-risk chronic hepatitis B patients in an attempt to prevent the progression of liver disease. We regarded at least 6 months as a significant duration of preemptive antiviral treatment before diagnosis of HCC. Results Of the 108 patients, 30 (27.8%) patients received preemptive antiviral therapy. Treatment-related decompensation was observed in 25 (23.1%) patients during the follow-up period. Treatment-related decompensation following TACE was observed more frequently in the nonpreemptive group than in the preemptive group (29.5% vs. 6.7%, P=0.008). In the multivariate analysis, higher serum total bilirubin (Hazard ratio [HR] =3.425, P=0.013), hypoalbuminemia (HR=3.990, P=0.015), and absence of antiviral therapy (HR=7.597, P=0.006) were significantly associated with treatment-related hepatic decompensation. Conclusion Our findings suggest that preemptive antiviral therapy significantly reduces the risk of acute hepatic deterioration. Preventing hepatic deterioration during TACE by applying such a preemptive approach may facilitate the continuation of anticancer therapy and thus improve long-term outcomes.

373 DISTRIBUTION PATTERNS OF SERUM HEPATITIS B SURFACE ANTIGEN LEVELS OVER THE NATURAL COURSE OF CHRONIC HEPATITIS B: THE ROLE OF AGE AND IMMUNE PHASE

Conclusion: HBsAg reversion occurs after renal transplantation with an incidence of 0.7 per 100 patient-year and is followed by reactivation. This intervenes mainly in the first post transplantation year. Ethnic background, acute rejection episodes, and absence of anti-HBs Ab before transplantation appear as risk factors for reactivation. Patients with resolved hepatitis B but without protective anti-HBs Ab should receive vaccination.

Early development of de novo hepatocellular carcinoma after direct-acting agent therapy: Comparison with pegylated interferon-based therapy in chronic hepatitis C patients

Patients with chronic hepatitis C who achieve a sustained viral response after pegylated interferon therapy have a reduced risk of hepatocellular carcinoma, but the risk after treatment with direct‐acting antivirals is unclear. We compared the rates of early development of hepatocellular carcinoma after direct‐acting antivirals and after pegylated interferon therapy. We retrospectively analysed 785 patients with chronic hepatitis C who had no history of hepatocellular carcinoma (211 treated with pegylated interferon, 574 with direct‐acting antivirals) and were followed up for at least 24 weeks after antiviral treatment. De novo hepatocellular carcinoma developed in 6 of 574 patients receiving direct‐acting antivirals and in 1 of 211 patients receiving pegylated interferon. The cumulative incidence of early hepatocellular carcinoma development did not differ between the treatment groups either for the whole cohort (1.05% vs 0.47%, P = .298) or for those patients with Child‐Pugh Class A cirrhosis (3.73% vs 2.94%, P = .827). Multivariate analysis indicated that alpha‐fetoprotein level >9.5 ng/mL at the time of end‐of‐treatment response was the only independent risk factor for early development of hepatocellular carcinoma in all patients (P < .0001, hazard ratio 176.174, 95% confidence interval 10.768‐2882.473) and in patients treated with direct‐acting agents (P < .0001, hazard ratio 128.402, 95% confidence interval 8.417‐1958.680). In conclusion, the rate of early development of hepatocellular carcinoma did not differ between patients treated with pegylated interferon and those treated with direct‐acting antivirals and was associated with the serum alpha‐fetoprotein level at the time of end‐of‐treatment response.

1033 COMBINATION THERAPY WITH TRANSARTERIAL CHEMOEMBOLIZATION AND RADIOFREQENCY ABLATION COMPARED WITH TRANSARTERIAL CHEMOEMBOLIZATION OR RFA FOR EARLY HEPATOCELLULAR CARCINOMA

1032 COMPARATIVE STUDY BETWEEN DRUG-ELUTING BEAD (DC BEAD) LOADED WITH DOXORUBICIN (DEBDOX) AND CONVENTIONAL TRANSARTERIAL CHEMOEMBOLIZATION IN THE TREATMENT OF HEPATOCELLULAR CARCINOMA M.J. Song, D.S. Song, S.H. Yoo, H.Y. Kim, C.-H. Park, U.I. Chang, H.J. Chun, S.H. Bae, J.Y. Choi, J.M. Yang, S.K. Yoon. Hepatology and Gastroenterology, Radiology, The Catholic Medical University, Seoul, Republic of Korea E-mail: mjsong95@gmail.com